Overview
Chromosome 17p deletion [del(17p)] refers to the loss of the short arm of chromosome 17 and is identified in approximately 10% of patients with early-stage multiple myeloma. This deletion involves a major portion of chromosome 17p and results in the loss of several critical genes, most notably the TP53 gene, which encodes the tumor suppressor protein p53.
The p53 protein plays a crucial role in regulating the cell cycle by preventing cells with damaged DNA from progressing from the G1 to the S phase. It is also involved in DNA repair and apoptosis. Loss or inactivation of p53 removes this protective mechanism, allowing damaged cells to proliferate, thereby promoting tumorigenesis.
Microdeletions in chromosomal regions 17p13.1, 17p13.2, and 17p13.3 are associated with a variety of genetic and clinical abnormalities. Deletions involving chromosome 17p are generally associated with poor prognosis and aggressive disease behavior.
Symptoms
Chromosome 17p deletion itself does not cause specific symptoms; rather, clinical manifestations arise from the associated diseases and syndromes. In hematological malignancies such as multiple myeloma and chronic lymphocytic leukemia (CLL), symptoms are related to rapid disease progression and treatment resistance.
In genetic microdeletion syndromes, clinical features may include intellectual disability, poor or absent speech, dysmorphic facial features, and microcephaly. Deletions involving 17p13.3 can lead to isolated lissencephaly sequence or Miller–Dieker syndrome, characterized by a smooth cerebral cortex, developmental delay, intellectual disability, and seizures. Learning difficulties and developmental delays are common across several 17p microdeletion disorders.
Causes
Chromosome 17p deletion occurs due to the loss of genetic material from the short arm of chromosome 17. This genetic abnormality can be acquired, as seen in cancers such as multiple myeloma, lymphoproliferative disorders, acute promyelocytic leukemia, and chronic lymphocytic leukemia, or it may be congenital, as observed in microdeletion syndromes.
Loss of TP53 function is a key molecular event associated with 17p deletion and plays a principal role in tumor development. Inactivation of the p53 gene has also been implicated in premalignant conditions such as actinic keratosis and malignancies like squamous cell carcinoma. Human chromosome 17 also contains other important genes, including BRCA1 and NF1, contributing to cancer susceptibility and genomic instability.
Risk Factors
Deletion of chromosome 17p is a high-risk genetic abnormality associated with poor prognosis across multiple conditions. In multiple myeloma, del(17p) is linked to aggressive disease and reduced survival. In chronic lymphocytic leukemia, it is found in 5–8% of patients requiring first-line treatment and is strongly associated with rapid disease progression and treatment resistance.
Patients with microdeletions involving 17p13 regions are at increased risk for neurodevelopmental disorders, intellectual disability, and congenital abnormalities. Overall, the presence of chromosome 17p deletion signifies a higher risk of disease severity and adverse clinical outcomes.
Prevention
There is no direct prevention for chromosome 17p deletion, as it represents a genetic abnormality. However, early detection and appropriate management can improve outcomes. Diagnostic methods for detecting 17p deletion include chromosome G-banding (karyotyping) and interphase fluorescence in situ hybridization (FISH). Somatic mutations involving the TP53 gene are identified using next-generation sequencing or Sanger sequencing.
Proper sample collection is essential for accurate diagnosis. Blood samples should be collected in sodium heparin tubes and kept at room temperature, while tissue samples may be submitted as paraffin blocks.
From a therapeutic perspective, patients with del(17p) or TP53 mutations benefit from targeted treatment strategies. Continuous therapy with Bruton’s tyrosine kinase (BTK) inhibitors has been shown to improve overall survival compared to conventional chemoimmunotherapy. In relapsed or refractory cases, combination chemoimmunotherapy regimens may be used effectively. Early genetic testing allows the timely initiation of appropriate therapies and helps guide prognosis and treatment planning.
